Paget’s disease is a condition involving focal overactivity of bone cells (osteoblasts and osteoclasts), which can result in significant skeletal morbidity. It is unclear in which bone cells the causative lesion resides. It is managed effectively with potent bisphosphonates, but treatment is difficult if these drugs are contraindicated. We describe a 75-year-old woman with Paget’s disease involving the skull who was intolerant of bisphosphonates, so was treated with denosumab. This intervention normalized serum alkaline phosphatase for 4–8 months after each injection and led to some symptomatic improvement. Scintigraphic activity in the lesion was improved but not normalized. We conclude that reduction in RANKL activity by denosumab only partially corrects pagetic activity, indicating that the osteoclast overactivity of Paget’s disease is not wholly mediated by RANKL. Denosumab has some clinical utility in Paget’s disease and may become a second-line agent in those with contraindications to intravenous bisphosphonates.
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Conflict of Interest
Dr. Reid reports grants, personal fees, and non-financial support from Amgen; grants, personal fees, and non-financial support from Novartis; grants and personal fees from Merck, outside the submitted work. Sonakshi Sharma, Ramanamma Kalluru, and Carl Eagleton have no conflict of interest to declare.
Human and Animal Rights and Informed Consent
The patient provided consent to receive treatment with denosumab for an unregistered inidcation and also consented to the publication of this case report.
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Reid, I.R., Sharma, S., Kalluru, R. et al. Treatment of Paget’s Disease of Bone with Denosumab: Case Report and Literature Review. Calcif Tissue Int 99, 322–325 (2016). https://doi.org/10.1007/s00223-016-0150-6
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